Mid-Career Funding Helps Scientists Answer Big Questions

It’s the unanswered questions that drive researchers Gypsyamber D’Souza and Ophir Klein. Their work—D’Souza’s public health study of oral cancer and Klein’s basic research on dental stem cells—requires quite different scientific approaches. But the scientists share a powerful urge to find answers to challenging problems that will ultimately improve human health.

Both D’Souza and Klein are established experts in their fields, having managed their own research groups for nearly a decade. By 2015 they had reached the point in their careers when many scientists—even the highly talented—struggle in an increasingly competitive funding environment that has made it harder to maintain dependable, continuous support.

Recognizing that enabling such scientists to focus on long-term goals could accelerate biomedical research breakthroughs in the future, NIDCR created the Sustaining Outstanding Achievement in Research (SOAR) award in 2015. SOAR awards provide up to 8 years of stable funding to a subset of mid-career scientists called early-established investigators—researchers within 10 years of receiving their first substantial, independent NIDCR research project grant who have outstanding records of research productivity, mentorship, and professional service to the research community.

The grants are designed to propel early-established researchers along their career trajectories and support ambitious, long-term research programs that have extraordinary potential. Other NIH institutes and centers offer similar early-stage and early-established career support to scientists. In August 2017, NIH launched the Next Generation Researchers Initiative to develop additional strategies to grow and retain talented scientists across critical career stages.

D’Souza, an associate professor of epidemiology and international health at Johns Hopkins University, and Klein, a professor of orofacial sciences and pediatrics at the University of California, San Francisco, are the first recipients of NIDCR’s SOAR awards. Both scientists cite the program as giving them freedom for in-depth, long-term exploration without the distractions and pressures that arise from needing to obtain funding every few years, as is typical in academia.

“The sustained support from SOAR has allowed me to live out my vision of how science should be, so I can commit my time to a public health issue I care about,” says D’Souza.

She’s examining the epidemiology of oral human papilloma virus (HPV) infection and the risk for HPV-associated oropharyngeal cancer, which affects the areas around the tonsils and base of tongue. HPV is the most common sexually transmitted infection in the US and can infect the genitals, mouth, and throat. Most HPV infections go away on their own, but some can cause cancer in the affected body region. HPV-associated oropharyngeal cancer has been on the rise in men.

D’Souza’s SOAR funding, awarded in September 2016, has allowed her to begin recruiting volunteers for a study that aims to determine why some people with oral HPV develop cancer while most others don’t. To figure out who’s most at risk for HPV-related oropharyngeal cancer, D’Souza needs to study a large group of people. It takes many years to plan, gather volunteers, and collect and analyze such data.

“SOAR funding has given me the incredible opportunity to design a study that takes a longer period of time to carry out,” she says. This high-risk, high-reward research, a hallmark of the SOAR program, has the potential to fill important gaps in knowledge about oral HPV infection.

With her collaborators, D’Souza aims to recruit up to 4,000 participants from multiple sites across the country and screen them for a range of molecular indicators (biomarkers) of HPV status. She and her colleagues hope to find biomarkers that most reliably predict whether an HPV infection will persist, progress, or go away. This knowledge could enable clinicians and public health officials to better identify people at greatest risk and then intervene earlier or even prevent cancer from developing.

It can take time for a clear picture to emerge for basic research questions as well. That’s the case for Klein, who is trying to identify the factors that enable some mammals, such as rodents, to evolve continuously growing adult teeth—an ability that humans and many other mammals lack. To explore this phenomenon, Klein is studying dental stem cells in mice and other rodents. His work could lay a foundation for stem cell-based therapies to regenerate teeth or other organs in humans.

Mouse incisors (the top and bottom front teeth) grow constantly because they contain two types of stem cells: epithelial and mesenchymal stem cells. In contrast, adult human teeth do not maintain epithelial stem cells. Mesenchymal stem cells from teeth can turn into a variety of cells, including bone, cartilage, muscle, and fat. Epithelial stem cells in teeth are less versatile, and can produce cells that make the hardest mineral in the body, enamel. In mice, Klein is studying the mechanics of stem-cell induced tooth growth and trying to identify the precise cocktail of stimuli—molecular, genetic, and environmental—that drives the process. He’s also looking at how progenitor cells, which ultimately give rise to stem cells, emerge in the embryo. “Understanding these phenomena could help us better understand if we could target tooth progenitors in humans to cure diseases,” he says.

Both investigators say that SOAR funding has been transformative for their careers. “This award lets you focus on what you should be doing, which is your science,” says Klein. “The portion of your time that was previously spent cobbling together resources to run your lab can now be used to mentor trainees and to read and write papers,” he adds.

D’Souza agrees. “I feel really fortunate to be able to answer the questions I’m passionate about and to contribute in a meaningful way to patients affected by these diseases,” she says. (Learn more or volunteer for her study).

Being able to fully devote themselves to impactful long-term research means these investigators will be more likely to achieve the goals that drew them to biomedical science in the first place—finding better ways to treat disorders and improve human health and well-being.​​​​